ABSTRACT American Indians and Alaska Native (AIAN) people are disproportionately affected by chronic pain conditions, including arthritis, diabetic neuropathy, and lower back pain. AIAN communities have also experienced harm as a result of pain solutions offered by Western medicine, such as prescription opioids, which have contributed to increased opioid misuse and mortality in AIAN people. Many AIAN people have turned to Native medicine and other non-Western approaches to pain management. Thirty-four states have legalized marijuana for medical use, while 12 states, and the District of Columbia, have legalized non-medical use, and cannabidiol (CBD) derived from hemp is no longer a controlled substance. Therefore, cannabis products are available to the majority of U.S. adults. 66% of adults think that cannabis provides pain relief, and 42% of medicinal marijuana users report using it to relieve pain. While initial evidence indicates that cannabis tetrahydrocannabinol [THC] has analgesic effects, the evidence for cannabis-associated reductions in pain intensity and interference (i.e., the extent to which pain interferes with functioning) is limited. There is very limited data about the effects of how a variety of cannabis products available on the legal market (e.g., different strains, methods of delivery) and patterns of use impact pain outcomes and the comorbidities (e.g., mental health, sleep) that are associated with pain. As a sovereign nation in Washington State, our Tribal partners developed the Qwibil Clinic, which advises patients on the use of cannabis for the management of pain and other medical problems. The Qwibil Clinic provides a unique opportunity to investigate the relationship between cannabis use, pain, and pain-related factors in an AIAN owned and operated clinic. We propose a mixed-methods embedded (QUANT+Qual) study to assess how cannabis impacts pain intensity and interference in a sample of n=350 patients seeking chronic pain treatment at the Qwibil Clinic. We will identify types and patterns of cannabis use that are associated with pain outcomes over 12-months of care. We will also determine whether the effect of cannabis on pain outcomes is mediated through known pain-related factors (i.e., negative affect, sleep problems, self-efficacy) over time. To supplement our quantitative methods, we will use qualitative interviews to explore how patients seeking care for pain experience cannabis and its impact on pain, including participants who differ by sex, race (AIAN, Non-AIAN), and type of cannabis used. Finally, we will provide opportunities for AIAN students enrolled in Washington State University medical, nursing, pharmacy, and prevention science graduate programs and Northwest Indian College undergraduate programs to receive training and mentorship in cannabis and pain research at the Qwibil Clinic, including training in qualitative and quantitative data collection and analysis and disseminatio...